West Nile virus (WNV), a mosquito-borne flavivirus, is endemic to South Africa. However, its contribution to acute febrile and neurological disease in hospitalized patients in South Africa is unknown. This study examined two patient cohorts for WNV using molecular testing and IgM serology with confirmation of serological results by viral neutralization tests (VNT) to address this knowledge gap. Univariate analysis was performed using collected demographic and clinical information to identify risk factors. In the first cohort, 219 cerebrospinal fluid (CSF) specimens from patients with acute neurological disease in Gauteng hospitals collected in January to June 2017 were tested for WNV. The study identified WNV in 8/219 (3.65%, 95.00% CI (1.59–7.07)) patients with unsolved neurological infections. The second cohort, from 2019 to 2021, included 441 patients enrolled between January and June with acute febrile or neurological disease from urban and rural sites in Gauteng and Mpumalanga provinces. West Nile virus was diagnosed in 40/441 (9.07%, 95.00% CI (6.73–12.12)) of patients, of which 29/40 (72.50%, 95.00% CI (56.11–85.40)) had neurological signs, including headaches, encephalitis, meningitis, and acute flaccid paralysis (AFP). Notably, most of the cases were identified in children although adolescents and senior adults had a significantly higher risk of testing WNV positive. This suggests a previously underestimated disease burden and that WNV might be underrecognized as a cause of febrile and neurological diseases in hospitalized patients in South Africa, especially in children. This emphasizes the importance of further research and awareness regarding arboviruses of public health concern.

Severe acute respiratory tract infections (SARIs) has been well described in South Africa with seasonal patterns described for influenza and respiratory syncytial virus (RSV), while others occur year-round (rhinovirus and adenovirus). This prospective syndromic hospital-based surveillance study describes the prevalence and impact of public interventions on the seasonality of other respiratory pathogens during the coronavirus disease-19 (COVID-19) pandemic. This occurred from August 2018 to April 2022, with 2595 patients who met the SARS case definition and 442 controls, from three sentinel urban and rural hospital sites in South Africa. Naso/oro-pharyngeal (NP/OP) swabs were tested using the FastTrack Diagnostics^® Respiratory pathogens 33 (RUO) kit. Descriptive statistics, odds ratios, and univariate/multivariate analyses were used. Rhinovirus (14.80%, 228/1540) and Streptococcus pneumoniae (28.50%, 439/1540) were most frequently detected in NP/OP swabs and in children <1 years old (35%, 648/1876). Among others, pathogens associated with SARI cases causing disease were influenza A&B, HRV, RSV, hCoV 229e, Haemophilus influenzae, Staphylococcus aureus, and Streptococcus pneumoniae. Pre-COVID-19, seasonal trends of these pathogens correlated with previous years, with RSV and influenza A seasons only resuming after the national lockdown (2021). It is evident that stringent lockdown conditions have severe impacts on the prevalence of respiratory tract infections.